Three models have been selected to evaluate the role of the spleen in immunoregulation: (1) the effect of splenectomy on first set skin allograft rejection across major and minor histocompatibility barriers; (2) the role of the spleen in promoting the immunologic privilege of tissues implanted in the anterior chamber of the rat's eye; (3) the role of splenic cells - lymphocytes and macrophages - in limiting the clonal expansion of histocompatibility antigen recognizing cells when confronted by appropriate alloantigens. These studies are predicated on the underlying hypothesis that the spleen is a major tissue site for the conversion of cell mediated to antibody mediated responses. In addition to identifying experimental evidence in support of this hypothesis, an analysis of the special properties which equip the spleen for this role will also be carried out. Three potential variables which will be pursued are (1) the ratio of T to B lymphocytes which is different in the spleen from other immunocompetent organs and favors the activation of B cells; (2) the production of special classes of antibody which fix complement poorly and function as enhancing antibodies; and (3) the differentiation of immature thymocytes into suppressor T cells in the splenic environment and/or the activation of a population of suppressor macrophages or B cells. BIBLIOGRAPHIC REFERENCES: Streilein, J.W., Duncan, W.R., and Thompson, S.A. SD Determinants and Failure of Cellular Collaboration in Hamsters. Transpl. Proc. IX: in press, 1977. Kaplan, H.J. and Streilein, J.W. Immunologic privilege within the anterior chamber of the eye. Transpl. Proc. IX: In press, 1977.